Measurable imaging-based changes in enhancement of intrahepatic cholangiocarcinoma after radiotherapy reflect physical mechanisms of response.

Background: Although escalated doses of radiation therapy (RT) for intrahepatic cholangiocarcinoma (iCCA) are associated with durable local control (LC) and prolonged survival, uncertainties persist regarding personalized RT based on biological factors. Compounding this knowledge gap, the assessment of RT response using traditional size-based criteria via computed tomography (CT) imaging correlates poorly with outcomes. We hypothesized that quantitative measures of enhancement would more accurately predict clinical outcomes than size-based assessment alone and developed a model to optimize RT. Methods: Pre-RT and post-RT CT scans of 154 patients with iCCA were analyzed retrospectively for measurements of tumor dimensions (for RECIST) and viable tumor volume using quantitative European Association for Study of Liver (qEASL) measurements. Binary classification and survival analyses were performed to evaluate the ability of qEASL to predict treatment outcomes, and mathematical modeling was performed to identify the mechanistic determinants of treatment outcomes and to predict optimal RT protocols. Results: Multivariable analysis accounting for traditional prognostic covariates revealed that percentage change in viable volume following RT was significantly associated with OS, outperforming stratification by RECIST. Binary classification identified ≥33% decrease in viable volume to optimally correspond to response to RT. The model-derived, patient-specific tumor enhancement growth rate emerged as the dominant mechanistic determinant of treatment outcome and yielded high accuracy of patient stratification (80.5%), strongly correlating with the qEASL-based classifier. Conclusion: Following RT for iCCA, changes in viable volume outperformed radiographic size-based assessment using RECIST for OS prediction. CT-derived tumor-specific mathematical parameters may help optimize RT for resistant tumors.

Circulating tumor DNA (ctDNA) as a biomarker of response to therapy in advanced Hepatocellular carcinoma treated with Nivolumab.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC). OBJECTIVE: This study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab. METHODS: We analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions. RESULTS: Of 44 patients, 77.3% were men with median age of 67 years. All but 3 patients had at least one alteration identified, and TP53 was the most commonly altered gene (52.3%). Median OS was 17.5 months (95% CI: 12.7, NA). Mutations involving PIK3CA, BRCA1, and CCND1 amplification were associated with shorter OS (P 0.0001, 0.0001 and 0.01, respectively). Median PFS time was 4.01 months (95% CI: 3.06, 9.33). Mutations involving KIT and PIK3CA were associated with shorter PFS (P 0.0001 and 0.0004, respectively), while mutation involving CTNNB1 were associated with longer PFS (p= 0.04). CONCLUSIONS: ctDNA profiling may provide a benefit for prediction of survival and progression of HCC patients treated with nivolumab. Future studies are needed for confirmation.

Certification and long-term stability monitoring of low-content folic acid and 5-methyltetrahydrofolate in human plasma certified reference material by isotope dilution ultra-high performance liquid chromatography/tandem mass spectrometry.

A reliable measurement of blood folate levels is necessary in the clinical field to prevent serious diseases such as cognitive impairment and neural tube defects. Herein, the certification of the low-content folic acid (FA) and 5-methyltetrahydrofolate (5-Me-THF) in human plasma certified reference material (KRISS CRM 111-01-018) was performed. A human plasma pool obtained from the Korean Red Cross was used as a CRM candidate. The certification of the human plasma CRM was performed by isotope dilution ultra-performance liquid chromatography/tandem mass spectrometry. Two-dimensional liquid chromatography was employed to confirm the validity of the analytical method for FA due to the susceptibility of FA to matrix effects because of its limited quantity. The CRM stability was evaluated at -20 °C for 2 months and at -70 °C for up to 12 months to determine the certified value of the CRM. The certified value of the CRM was (84.6 ± 4.3) ng kg-1 and (5.80 ± 0.47) µg kg-1 for FA and 5-Me-THF, respectively. The homogeneity of the CRM was 1.64% and 3.10% for FA and 5-Me-THF, respectively. Further long-term stability assessments were conducted, indicating that the CRM remains valid for at least 58 months at -70 °C for FA and 48 months for 5-Me-THF. Compared to other blood-based CRMs, this CRM has lower folate levels, making it helpful in establishing analytical methods for a broader range of folate levels.

Unveiling crystal orientation-dependent interface property in composite cathodes for solid-state batteries by in situ microscopic probe.

A critical bottleneck toward all-solid-state batteries lies in how the solid(electrode)-solid(electrolyte) interface is fabricated and maintained over repeated cycles. Conventional composite cathodes, with crystallographically distinct electrode/electrolyte interfaces of random particles, create complexities with varying (electro)chemical compatibilities. To address this, we employ an epitaxial model system where the crystal orientations of cathode and solid electrolyte are precisely controlled, and probe the interfaces in real-time during co-sintering by in situ electron microscopy. The interfacial reaction is highly dependent on crystal orientation/alignment, especially the availability of open ion channels. Interfaces bearing open ion paths of NCM are more susceptible to interdiffusion, but stabilize with the early formed passivation layer. Conversely, interfaces with closed ion pathway exhibit stability at intermediate temperatures, but deteriorate rapidly at high temperature due to oxygen evolution, increasing interfacial resistance. The elucidation of these distinct interfacial behaviors emphasizes the need for decoupling collective interfacial properties to enable rational design in solid-state batteries.

Study on Betaine and Growth Characteristics of Lycium chinense Mill. in Different Cultivation Environments in South Korea.

Betaine is a useful compound that has various activities and is the marker compound of Lycium chinense fruit in Korean Pharmacopoeia. we seek to support the stable production of medicinal goji berries, which have significant potential in the pharmaceutical industry due to their high values, and to provide foundational data for consistent quality control. This study's purpose was to examine the correlation among betaine content, environmental variables, and the growth characteristics of L. chinense fruits. The fruits were collected from 25 cultivation sites across South Korea. We investigated five growth characteristics and betaine contents in L. chinense fruits and twelve soil physicochemical properties, and seven meteorological data at cultivation sites. The fruit's growth characteristics included a length of 15.62-26.49 mm, a width of 7.09-11.38 mm, a fresh weight of 0.73-1.62 g, and a sugar content of 11.10-19.62 Brix°. Its betaine content ranged from 0.54% to 0.97%. The betaine content was positively correlated with electrical conductivity (0.327 **), exchangeable potassium (0.314 **), and sodium (0.259 *) and negatively correlated with annual average minimum temperature (-0.256 *) and annual average temperature (-0.242 *). Also, betaine showed a positive correlation with the length of the fruit (0.294 *) and the fresh weight of the fruit (0.238 *). These results can be used to find the best cultivation method and to manage quality control for the highly economical L. chinense fruit.

Effectiveness of organic acids for inactivating pathogenic bacteria inoculated in laboratory media and foods: an updated minireview.

Food processing industries commonly employ organic acids (OAAs) to determine bacterial contamination in acidified and fermented foods. OAAs are believed to possess potent antimicrobial properties by permeating cell membranes, altering proton and anion concentrations in the cytoplasm due to their lipophilic undissociated forms. The bacteriostatic or bactericidal effects of OAAs are influenced by various factors including microbial physiology, environmental pH, and acid dissociation ratios. Despite their utility, the precise mechanisms underlying OAA-mediated inhibition of pathogenic bacteria remain incompletely understood. Therefore, the objectives of this review are to compile a selected area of researches that focus on the current propensity of different OAAs for inactivating food-borne pathogens, and then to present a theoretical insight on the use of OAAs to prevent and control pathogenic bacteria present in acidic/acidified foods and their mode of mechanisms.

Control of Escherichia coli O157:H7, Salmonella enterica serovar Typhimurium, and Listeria monocytogenes inoculated in beetroot or watermelon juice by combined treatments with organic acid or lemon (Citrus limon) extract and mild heat.

The study aimed to evaluate the synergistic interaction of organic acids (OAAs) or lemon extract (LE) plus mild heat (MH; 55 °C) against Escherichia coli O157:H7, Salmonella enterica serovar Typhimurium, and Listeria monocytogenes inoculated in beetroot and watermelon juices. A mixed culture cocktail of E. coli O157:H7, S. Typhimurium or L. monocytogenes was inoculated in beetroot or watermelon juice, followed by treatments with MH, citric acid + MH, malic acid + MH, tartaric acid + MH, and LE + MH. Approximately < 2.0-log reductions in the number of E. coli O157:H7, S. Typhimurium, and L. monocytogenes were observed when these bacteria were heated in juices at 55 °C for 5 min. A combination of 1.0% OAAs or 20% LE and MH (55 °C) for 5 min resulted in an additional log-reduction in the count of E. coli O157:H7, S. Typhimurium, and L. monocytogenes by 2.2-5.0, 4.5-5.0, and 1.5-5.0, respectively.

Contrast-Enhanced T1-Weighted Magnetic Resonance Cholangiography Using Gadoxetate Disodium in Potential Living Liver Donors: Qualitative and Quantitative Improvement with 3-hour Delayed Imaging.

BACKGROUND: Contrast-enhanced T1-weighted magnetic resonance cholangiography (CE-T1-MRC) after gadoxetate disodium administration can be used for preoperative evaluation of the bile ducts in live liver donors. This study aimed to determine whether CE-T1-MRC with 3-hour delayed imaging improves bile duct visualization both qualitatively and quantitatively compared with 20-minute delayed imaging in potential living liver donors. METHODS: We retrospectively identified 33 potential living liver donors (mean age, 30.1 years; 18 men and 15 women) who underwent preoperative CE-T1-MRC with both 20-minute delayed and 3-hour delayed imaging in a single session. The radiologist scored biliary visualization for right and left hepatic ducts (RHD and LHD), their secondary confluences and segmental bile ducts, common hepatic duct (CHD), and cystic duct (CD), and measured relative contrast ratio (rC) and relative signal intensity (rS) for RHD, LHD, and CHD. The data were analyzed using Wilcoxon's signed-rank test and paired t-test. RESULTS: In qualitative analysis, duct visualization scores for RHD and LHD, their secondary confluences and segmental bile ducts, CHD, and CD were significantly higher on CE-T1-MRC with 3-hour delayed imaging than with 20-minute delayed imaging (all, P ≤ .046). In quantitative analysis, both rC and rS of RHD, LHD, and CHD were significantly higher on CE-T1-MRC with 3-hour delayed imaging than with 20-minute delayed imaging (all, P < .001). CONCLUSIONS: CE-T1-MRC with 3-hour delay imaging improves bile duct visualization both qualitatively and quantitatively in potential living liver donors.

Addition of Metastasis-Directed Therapy to Systemic Therapy for Oligometastatic Pancreatic Ductal Adenocarcinoma (EXTEND): A Multicenter, Randomized Phase II Trial.

PURPOSE: The EXTEND trial tested the hypothesis that adding comprehensive metastasis-directed therapy (MDT) to chemotherapy would improve progression-free survival (PFS) over chemotherapy alone among patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC). METHODS: EXTEND (ClinicalTrials.gov identifier: NCT03599765) is a multicenter, phase II basket trial randomly assigning patients with ≤five metastases 1:1 to MDT plus systemic therapy versus systemic therapy. Disease progression was defined by radiologic criteria (RECIST v1.1), clinical progression, or death. The primary end point was PFS in the per-protocol population, evaluated after all patients achieved at least 6 months of follow-up. Exploratory end points included systemic immune response measures. RESULTS: Between March 19, 2019, and February 13, 2023, 41 patients were randomly assigned and 40 were eligible for the primary analysis of PFS (19 patients in the MDT arm; 21 patients in the control arm). At a median follow-up time of 17 months, the median PFS time was 10.3 months (95% CI, 4.6 to 14.0) in the MDT arm versus 2.5 months (95% CI, 1.7 to 5.1) in the control arm. PFS was significantly improved by the addition of MDT to systemic therapy (P = .030 for stratified log-rank test) with a hazard ratio of 0.43 (95% CI, 0.20 to 0.94). No grade ≥3 or greater adverse events related to MDT were observed. Systemic immune activation events were associated with MDT and correlated with improved PFS. CONCLUSION: This study supports the addition of MDT to systemic therapy for patients with oligometastatic PDAC. Induction of systemic immunity is a possible mechanism of benefit. These results warrant confirmatory trials to refine treatment strategy and provide external validation.

Intraindividual comparison of prognostic imaging features of HCCs between MRIs with extracellular and hepatobiliary contrast agents.

BACKGROUND & AIMS: Accumulating evidence suggests that certain imaging features of hepatocellular carcinoma (HCC) may have prognostic implications. This study aimed to intraindividually compare MRIs with extracellular contrast agent (ECA-MRI) and hepatobiliary agent (HBA-MRI) for prognostic imaging features of HCC and to compare the prediction of microvascular invasion (MVI) and early recurrence between the two MRIs. METHODS: The present study included 102 prospectively enrolled at-risk patients (median age, 61.0 years; 83 men) with surgically resected single HCC with both preoperative ECA-MRI and HBA-MRI between July 2019 and June 2023. The McNemar test was used to compare each prognostic imaging feature between the two MRIs. Significant imaging features associated with MVI were identified by multivariable logistic regression analysis, and early recurrence rates (<2 years) were compared between the two MRIs. RESULTS: The frequencies of prognostic imaging features were not significantly different between the two MRIs (p = .07 to >.99). Non-smooth tumour margin (ECA-MRI, odds ratio [OR] = 5.30; HBA-MRI, OR = 7.07) and peritumoral arterial phase hyperenhancement (ECA-MRI, OR = 4.26; HBA-MRI, OR = 4.43) were independent factors significantly associated with MVI on both MRIs. Two-trait predictor of venous invasion (presence of internal arteries and absence of hypoattenuating halo) on ECA-MRI (OR = 11.24) and peritumoral HBP hypointensity on HBA-MRI (OR = 20.42) were other predictors of MVI. Early recurrence rates of any two or more significant imaging features (49.8% on ECA-MRI vs 51.3% on HBA-MRI, p = .75) were not significantly different between the two MRIs. CONCLUSION: Prognostic imaging features of HCC may be comparable between ECA-MRI and HBA-MRI.

Exploring the impact of excluding intrahepatic segmental vessels on liver stiffness measurement and advanced fibrosis diagnosis using magnetic resonance elastography.

BACKGROUND: The impact of excluding intrahepatic segmental vessels from regions of interest (ROIs) on liver stiffness measurement (LSM) via magnetic resonance elastography (MRE) remains uncertain. PURPOSE: To determine the effect of excluding intrahepatic segmental vessels from ROIs on LSM obtained from MRE. MATERIAL AND METHODS: This retrospective analysis included 95 participants who underwent successful two-dimensional gradient recalled-echo MRE before hepatic tumor resection (n = 49) or living liver donation (n = 46). The conventional LSM was determined by manually drawing ROIs on the elastogram within the 95% confidence region, staying 1 cm within the liver capsule and excluding large hilar vessels, the gallbladder, hepatic lesions, and artifacts. In addition, the modified LSM was determined by excluding intrahepatic segmental vessels. LSMs obtained by the two methods were compared with paired sample signed-rank test. Diagnostic performance for advanced fibrosis was calculated and compared using McNemar's test and Delong's test. The stage of hepatic fibrosis was assessed using surgical specimens by the METAVIR system. RESULTS: The modified LSM was larger than the conventional LSM (2.4 kPa vs. 2.2 kPa in reader 1; 2.7 kPa vs. 2.4 kPa in reader 2; P < 0.001). The modified LSM showed superior sensitivity (0.841 vs. 0.659 in reader 1; 0.864 vs. 0.705 in reader 2; P < 0.05) and area under the curve (0.901 vs. 0.820 in reader 1; 0.912 vs. 0.843 in reader 2; P < 0.05) for detecting advanced fibrosis (≥F3) than conventional LSM. CONCLUSION: The exclusion of intrahepatic segmental vessels from ROIs in MRE affected the LSM and enhanced diagnostic performance for advanced fibrosis.

Genomic Biomarkers to Predict Response to Atezolizumab Plus Bevacizumab Immunotherapy in Hepatocellular Carcinoma: Insights from the IMbrave150 Trial.

Introduction: Combination immunotherapy, exemplified by atezolizumab plus bevacizumab, has become the standard of care for inoperable hepatocellular carcinoma (HCC). However, the lack of predictive biomarkers and limited understanding of response mechanisms remain a challenge. Methods: Using data from the IMbrave150plus cohort, we applied an immune signature score (ISS) predictor to stratify HCC patients treated with atezolizumab plus bevacizumab or with sorafenib alone into potential high and low response groups. By applying multiple statistical approaches including a Bayesian covariate prediction algorithm, we refined the signature to 10 key genes (ISS10) for clinical use while maintaining similar predictive power to the full model. We further validated ISS10 in an independent HCC cohort treated with nivolumab plus ipilimumab. Results: The study identified a significant association between the ISS and treatment response. Among patients classified as high responders, those treated with the atezolizumab plus bevacizumab combination exhibited improved overall and progression-free survival as well as better objective response rate compared to those treated with sorafenib. We also observed a significant correlation between ISS10 and response to nivolumab plus ipilimumab treatment. Analysis of immune cell subpopulations revealed distinct characteristics associated with ISS subtypes. In particular, the ISS10 high subtype displayed a more favorable immune environment with higher proportions of anti-tumor macrophages and activated T-cells, potentially explaining its better response. Conclusions: Our study suggests that ISS and ISS10 are promising predictive biomarkers for enhanced therapeutic outcomes in HCC patients undergoing combination immunotherapy. These markers are crucial for refining patient stratification and personalized treatment approaches to advance the effectiveness of standard-of-care regimens.

Escalated-dose radiotherapy for unresected locally advanced pancreatic cancer: Patterns of care and survival in the United States.

INTRODUCTION: With locally advanced pancreatic cancer (LAPC), uncontrolled local tumor growth frequently leads to mortality. Advancements in radiotherapy (RT) techniques have enabled conformal delivery of escalated-dose RT (EDR), which may have potential local control and overall survival (OS) benefits based on retrospective and early prospective studies. With evidence for EDR emerging, we characterized the adoption of EDR across the United States and its associated outcomes. METHODS: We searched the National Cancer Database for nonsurgically managed LAPC patients diagnosed between 2004 and 2019. Pancreas-directed RT with biologically effective doses (BED10) ≥39 and ≤70 Gy was labeled conventional-dose RT (CDR), and BED10 >70 and ≤132 Gy was labeled EDR. We identified associations of EDR and OS using logistic and Cox regressions, respectively. RESULTS: Among the definitive therapy subset (n = 54,115) of the entire study cohort (n = 91,493), the most common treatments were chemotherapy alone (69%), chemotherapy and radiation (29%), and RT alone (2%). For the radiation therapy subset (n = 16,978), use of pancreas-directed RT remained between 13% and 17% over the study period (ptrend > 0.999). Using multivariable logistic regression, treatment at an academic/research facility (adjusted odds ratio [aOR] 1.46, p < 0.001) and treatment between 2016 and 2019 (aOR 2.54, p < 0.001) were associated with greater receipt of EDR, whereas use of chemotherapy (aOR 0.60, p < 0.001) was associated with less receipt. Median OS estimates for EDR and CDR were 14.5 months and 13.0 months (p < 0.0001), respectively. For radiation therapy subset patients with available survival data (n = 13,579), multivariable Cox regression correlated EDR (adjusted hazard ratio 0.85, 95% confidence interval 0.80-0.91; p < 0.001) with longer OS versus CDR. DISCUSSION AND CONCLUSIONS: Utilization of EDR has increased since 2016, but overall utilization of RT for LAPC has remained at less than one in five patients for almost two decades. These real-world results additionally provide an estimate of effect size of EDR for future prospective trials.

Bintrafusp alfa and chemotherapy as first-line treatment in biliary tract cancer: A randomized phase 2/3 trial.

BACKGROUND AND AIMS: We compared the safety and efficacy of bintrafusp alfa (BA) in combination with gemcitabine+cisplatin (GemCis), to those of GemCis alone, in patients with biliary tract cancer. APPROACH AND RESULTS: This randomized, double-blind, placebo-controlled, adaptive design phase 2/3 trial (NCT04066491) included adults who are treatment-naive with locally advanced/metastatic biliary tract cancer. Patients (N = 297) were randomized to receive an IV infusion of BA (2400 mg once/3 wk) plus GemCis (gemcitabine 1000 mg/m 2 +cisplatin 25 mg/m 2 on days 1 and 8/3 wk; 8 cycles) (BA group, n = 148) or placebo+GemCis (placebo group, n = 149). The primary end point was overall survival (OS). For adaptation analysis (phase 2-phase 3; data cutoff: May 20, 2021), efficacy was assessed in the first 150 patients who were antibiotic-naive when 80 progression-free survival events had occurred and ≥ 19 weeks of follow-up had been completed (BA, n = 73; placebo, n = 77). Median OS (95% CI) for the BA (11.5 mo [9.3-not estimable]) and placebo (11.5 mo [10.0-not estimable]) groups was comparable (hazard ration 1.23 [95% CI 0.66-2.28]; p = 0.7394); OS data maturity was 27.2% (41 events/151 patients). The most common grade ≥3 treatment-related adverse event was anemia (BA, 26.0%; placebo, 22.8%). Bleeding adverse events were reported more frequently in the BA group (28.8%) versus the placebo group (7.4%). Deaths within 60 days of the first dose were reported in 7.5% and 1.3% of patients in the BA and placebo groups, respectively. CONCLUSIONS: BA+GemCis did not provide a clinically meaningful benefit compared with GemCis alone as first-line treatment for biliary tract cancer, and the study was discontinued early (terminated: August 20, 2021).

Phase I trial of single-photon emission computed tomography-guided liver-directed radiotherapy for patients with low functional liver volume.

BACKGROUND: Traditional constraints specify that 700 cc of liver should be spared a hepatotoxic dose when delivering liver-directed radiotherapy to reduce the risk of inducing liver failure. We investigated the role of single-photon emission computed tomography (SPECT) to identify and preferentially avoid functional liver during liver-directed radiation treatment planning in patients with preserved liver function but limited functional liver volume after receiving prior hepatotoxic chemotherapy or surgical resection. METHODS: This phase I trial with a 3 + 3 design evaluated the safety of liver-directed radiotherapy using escalating functional liver radiation dose constraints in patients with liver metastases. Dose-limiting toxicities were assessed 6-8 weeks and 6 months after completing radiotherapy. RESULTS: All 12 patients had colorectal liver metastases and received prior hepatotoxic chemotherapy; 8 patients underwent prior liver resection. Median computed tomography anatomical nontumor liver volume was 1584 cc (range = 764-2699 cc). Median SPECT functional liver volume was 1117 cc (range = 570-1928 cc). Median nontarget computed tomography and SPECT liver volumes below the volumetric dose constraint were 997 cc (range = 544-1576 cc) and 684 cc (range = 429-1244 cc), respectively. The prescription dose was 67.5-75 Gy in 15 fractions or 75-100 Gy in 25 fractions. No dose-limiting toxicities were observed during follow-up. One-year in-field control was 57%. One-year overall survival was 73%. CONCLUSION: Liver-directed radiotherapy can be safely delivered to high doses when incorporating functional SPECT into the radiation treatment planning process, which may enable sparing of lower volumes of liver than traditionally accepted in patients with preserved liver function. TRIAL REGISTRATION: NCT02626312.

Imaging classification of pancreatic ductal adenocarcinoma with histological large duct pattern.

OBJECTIVES: To investigate the imaging features of pancreatic ductal adenocarcinoma (PDAC) with histological large duct pattern. METHODS: Our study included 37 patients (mean age, 66.5 years; 22 women) with surgically proven PDAC with histological large duct pattern, whose imaging features were classified into four types: Type I, solid mass; Type II, predominantly cystic mass with intracystic solid components; Type III, predominantly solid mass with intratumoral cysts; and Type IV, solid mass with peritumoral retention cysts or pseudocysts. Two radiologists independently analyzed both CT and MRI images for the morphological type, presence of abrupt main pancreatic duct (MPD) cutoff, adjacent vascular invasion, diffusion restriction, and reached consensus. RESULTS: On CT, 26 patients (70.3%) had Type I tumors, five (13.5%) had Type II, three (8.1%) had Type III, and three (8.1%) had Type IV. Among the 26 patients with Type I tumors on CT, 16 had tumors with multiple intratumoral cysts within the solid mass on MRI and were subsequently classified as Type III. Accordingly, 10 patients (27.0%) were classified as Type I, five (13.5%) as Type II, 19 (51.7%) as Type III, and three (8.1%) as Type IV on MRI. Of the 37 patients, 27 (73.0%) had an abrupt MPD cutoff, 15 (40.5%) had adjacent vascular invasion, and 25 (67.6%) had diffusion restriction on MRI. CONCLUSIONS: Predominantly solid pancreatic masses with small intratumoral cysts visualized on MRI may be a characteristic imaging finding of PDAC with histological large duct pattern, and differentiate it from conventional PDAC or other cystic pancreatic tumors. CLINICAL RELEVANCE STATEMENT: Radiologists should be familiar with the various imaging features of PDAC with histological large duct pattern and should be aware that it may mimic other solid or cystic tumors of the pancreas. KEY POINTS: Imaging features of pancreatic ductal adenocarcinoma with histological large duct pattern can be classified into four types. This pathology more frequently appears as a predominantly solid mass with intratumoral cysts on MRI than on CT. Adding MRI to CT may help identify pancreatic ductal adenocarcinoma with histological large duct pattern.

Performance of LI-RADS category 5 vs combined categories 4 and 5: a systemic review and meta-analysis.

OBJECTIVE: Computed tomography (CT)/magnetic resonance imaging (MRI) Liver Imaging Reporting and Data System (LI-RADS, LR) category 5 has high specificity and modest sensitivity for diagnosis of hepatocellular carcinoma (HCC). The purpose of this study was to compare the diagnostic performance of LR-5 vs combined LR-4 and LR-5 (LR-4/5) for HCC diagnosis. METHODS: MEDLINE and EMBASE databases through January 03, 2023 were searched for studies reporting the performance of LR-5 and combined LR-4/5 for HCC diagnosis, using CT/MRI LI-RADS version 2014, 2017, or 2018. A bivariate random-effects model was used to calculate the pooled per-observation diagnostic performance. Subgroup analysis was performed based on imaging modalities and type of MRI contrast material. RESULTS: Sixty-nine studies (15,108 observations, 9928 (65.7%) HCCs) were included. Compared to LR-5, combined LR-4/5 showed significantly higher pooled sensitivity (83.0% (95% CI [80.3-85.8%]) vs 65.7% (95% CI [62.4-69.1%]); p < 0.001), lower pooled specificity (75.0% (95% CI [70.5-79.6%]) vs 91.7% (95% CI [90.2-93.1%]); p < 0.001), lower pooled positive likelihood ratio (3.60 (95% CI [3.06-4.23]) vs 6.18 (95% CI [5.35-7.14]); p < 0.001), and lower pooled negative likelihood ratio (0.22 (95% CI [0.19-0.25]) vs 0.38 (95% CI [0.35-0.41]) vs; p < 0.001). Similar results were seen in all subgroups. CONCLUSIONS: Our meta-analysis showed that combining LR-4 and LR-5 would increase sensitivity but decrease specificity, positive likelihood ratio, and negative likelihood ratio. These findings may inform management guidelines and individualized management. CLINICAL RELEVANCE STATEMENT: This meta-analysis estimated the magnitude of changes in the sensitivity and specificity of imaging criteria when LI-RADS categories 4 and 5 were combined; these findings can inform management guidelines and individualized management. KEY POINTS: There is no single worldwide reporting system for liver imaging, partly due to regional needs. Combining LI-RADS categories 4 and 5 increased sensitivity and decreased specificity and positive and negative likelihood ratios. Changes in the sensitivity and specificity of imaging criteria can inform management guidelines and individualized management.

Differences in the prevalence of NAFLD, MAFLD, and MASLD according to changes in the nomenclature in a health check-up using MRI-derived proton density fat fraction.

PURPOSE: International expert panels proposed new nomenclatures, metabolic dysfunction-associated fatty liver disease (MAFLD) in 2020 and metabolic dysfunction-associated steatotic liver disease (MASLD) in 2023, along with revised diagnostic criteria to replace non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the differences in NAFLD, MAFLD, and MASLD prevalence with changing nomenclature in a health check-up using magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) to assess hepatic steatosis. We also examined the prevalence of the sub-classifications of steatotic liver disease (SLD) and the differences in characteristics among the sub-categories. METHODS: We included 844 participants who underwent liver MRI-PDFF at our health check-up clinic between January 2020 and November 2022. Hepatic steatosis was defined as MRI-PDFF ≥ 5%. Participants were categorized according to NAFLD, MAFLD, MASLD, and sub-classifications of SLD. RESULTS: The prevalence rates of NAFLD, MAFLD, and MASLD were 25.9%, 29.5%, and 25.2%, respectively. 30.5% of the participants was categorized as SLD. The prevalence rates of the SLD sub-categories were 25.2% for MASLD, 3.7% for MASLD and alcohol-associated liver disease (MetALD), 0.1% for alcohol-associated liver disease, 1.3% for specific etiology SLD, and 0.1% for cryptogenic SLD. Compared with patients in the MASLD group, those in the MetALD group were younger, predominantly male, and exhibited higher levels of serum aspartate aminotransferase, gamma-glutamyl transpeptidase, and triglycerides. CONCLUSION: The prevalences of NAFLD and MASLD assessed using MRI-PDFF were similar, with MASLD accounting for 97.3% of the patients with NAFLD. The separate MetALD sub-category may have clinical characteristics that differ from those of MASLD.

Application of sodium alginate-based edible coating with citric acid to improve the safety and quality of fresh-cut melon (Cucumis melo L.) during cold storage.

The safety and quality of fresh-cut melons is reduced by a series of decay processes by enzymatic browning and microbial contamination. This study aimed to assess the impact of a 2% sodium alginate-based edible coating (ALC) combined with different concentrations of citric acid (CA; 0.5%, 1%, 2%, and 3%) on the microbial safety and physical quality of fresh-cut melons during a 7-day storage period at 10 °C. The findings revealed that the combination of ALC and 3% CA was successful in preventing the growth of pathogenic bacteria (Escherichia coli O157:H7, Salmonella spp., Listeria monocytogenes, and Staphylococcus aureus) and natural microflora on fresh-cut melons during storage. In addition, treating fresh-cut melons with ALC containing 3% CA improved their quality by reducing browning and softening during storage at 10 °C. Based on these findings, it can be concluded that using ALC with 3% CA is an effective method to improve the safety and quality of fresh-cut melons.